Many reports have demonstrated 2-staged (or multi-staged) carcinogenesis in several animal systems. We have developed an in vitro Chinese hamster cell system which can distinguish carcinogenic agents which act either as mutagens (initiators) or gene modulators (promoters or anti-promoters). We propose to verify the potential of this in vitro assay system by (a) systematically testing a number of known tumor promoters and anti-promoters; (b) correlating the mutation modifying experiments with the induction or repression of ornithine decarboxylase; (c) studying the possible biochemical mechanism(s) of tumor promotion and anti-promotion; (d) studying the phenomenon of "co-mutagenesis" to see if it might be correlated with "co-carcinogenesis"; (e) applying the in vitro mutation assay to determine its practical potential (i.e., to test saccharine); and developing a human fibroblast assay system to be analogous to the Chinese hamster system.